{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:18:06Z","timestamp":1791415086087,"version":"4.3.3"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,5,14]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Mitochondria are key players in the development and progression of heart failure (HF). Mitochondrial (mt) dysfunction leads to diminished energy production and increased cell death contributing to the progression of left ventricular failure. The fundamental mechanisms that underlie mt dysfunction in HF have not been fully elucidated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              To characterize mt morphology, biogenesis, and genomic integrity in human HF, we investigated left ventricular tissue from nonfailing hearts and end-stage ischemic (ICM) or dilated (DCM) cardiomyopathic hearts. Although mt dysfunction was present in both types of cardiomyopathy, mt were smaller and increased in number in DCM compared with ICM or nonfailing hearts. mt volume density and mtDNA copy number was increased by \u22482-fold (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) in DCM hearts in comparison with ICM hearts. These changes were accompanied by an increase in the expression of mtDNA-encoded genes in DCM versus no change in ICM. mtDNA repair and antioxidant genes were reduced in failing hearts, suggestive of a defective repair and protection system, which may account for the 4.1-fold increase in mtDNA deletion mutations in DCM (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05 versus nonfailing hearts,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05 versus ICM).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>In DCM, mt dysfunction is associated with mtDNA damage and deletions, which could be a consequence of mutating stress coupled with a peroxisome proliferator-activated receptor \u03b3 coactivator 1\u03b1\u2013dependent stimulus for mt biogenesis. However, this maladaptive compensatory response contributes to additional oxidative damage. Thus, our findings support further investigations into novel mechanisms and therapeutic strategies for mt dysfunction in DCM.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.112.001219","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T01:50:01Z","timestamp":1366077001000},"page":"1957-1967","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":95,"title":["Divergent Mitochondrial Biogenesis Responses in Human Cardiomyopathy"],"prefix":"10.1161","volume":"127","author":[{"given":"Preeti","family":"Ahuja","sequence":"first","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Wanagat","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibin","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Liem","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Ping","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor A.","family":"Antoshechkin","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B.","family":"Margulies","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Robb","family":"MacLellan","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Laboratories, Department of Medicine (P.A., J.W., W.R.M.), Division of Geriatrics (J.W.), Department of Anesthesiology (Z.W., Y.W.), and Department of Physiology (D.A.L., P.P.), David Geffen School of Medicine at UCLA, Los Angeles, CA; the Division of Biology; California Institute of Technology; Pasadena, CA (I.A.A.); and the Department of Medicine, University of Pennsylvania, Philadelphia, (K.B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(02)00184-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-007-9079-1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-8932(02)76802-4"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.04.110188.001445"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24405"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.65.092101.142705"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.04.002"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38331"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603615103"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.045104"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.06.035"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circheartfailure.108.812099"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.212753"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/290457a0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.7915"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.09.010"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.40.1177"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn280"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02255913"},{"key":"e_1_3_4_21_2","first-page":"143","author":"Sheehan DC","year":"1980","unstructured":"Sheehan DC. 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